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PMID: 26143512 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

NR2B subunit in the prefrontal cortex: A double-edged sword for working memory function and psychiatric disorders.

Neuroscience and biobehavioral reviews ·Vol. 56 ·2015-09-00 ·Pages 127-38

Monaco SA, Gulchina Y, Gao WJ

Abstract

The prefrontal cortex (PFC) is a brain region featured with working memory function. The exact mechanism of how working memory operates within the PFC circuitry is unknown, but persistent neuronal firing recorded from prefrontal neurons during a working memory task is proposed to be the neural correlate of this mnemonic encoding. The PFC appears to be specialized for sustaining persistent firing, with N-methyl-D-aspartate (NMDA) receptors, especially slow-decay NR2B subunits, playing an essential role in the maintenance of sustained activity and normal working memory function. However, the NR2B subunit serves as a double-edged sword for PFC function. Because of its slow kinetics, NR2B endows the PFC with not only "neural psychic" properties, but also susceptibilities for neuroexcitotoxicity and psychiatric disorders. This review aims to clarify the interplay among working memory, the PFC, and NMDA receptors; demonstrate the importance of NR2B in the maintenance of persistent activity; understand the risks and vulnerabilities of how NR2B is related to the development of neuropsychiatric disorders; identify gaps that currently exist in our understanding of these processes; and provide insights regarding future directions that may clarify these issues. We conclude that the PFC is a specialized brain region with distinct delayed maturation, unique neuronal circuitry, and characteristic NMDA receptor function. The unique properties and development of NMDA receptors, especially enrichment of NR2B subunits, endow the PFC with not only the capability to generate sustained activity for working memory, but also serves as a major vulnerability to environmental insults and risk factors for psychiatric disorders.

Keywords
NMDA receptors Neuron development Prefrontal cortex Psychiatric disorders Schizophrenia Working memory
MeSH Terms
Animals Humans Memory, Short-Term/physiology Mental Disorders/pathology Peptide Fragments/metabolism Prefrontal Cortex/metabolism Receptors, N-Methyl-D-Aspartate/metabolism
Chemicals
NR2B protein (1292-1308) Peptide Fragments Receptors, N-Methyl-D-Aspartate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Monaco Sarah A
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Room 243, Philadelphia, PA 19129, United States.
Gulchina Yelena
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Room 243, Philadelphia, PA 19129, United States.
Gao Wen-Jun
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Room 243, Philadelphia, PA 19129, United States. Electronic address: [email protected].
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Article Info
Journal
Neuroscience and biobehavioral reviews
Abbr.
Neurosci Biobehav Rev
ISSN
1873-7528
DOI
10.1016/j.neubiorev.2015.06.022
Email
[email protected]
Published
2015-09-00
Epub
2015-00-02
Pages
127-38
Language
English
Region
United States
NLM ID
7806090
PMCID
PMC4567400
Subset
IM
Grants
NIMH NIH HHS · R01 MH085666 · United States
NIMH NIH HHS · R01MH085666 · United States
External Links
PubMed source DOI: 10.1016/j.neubiorev.2015.06.022 PMC Full Text View journal details
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